Type 2 diabetes and pre-diabetes control, prevention, and reversal/remission

Table of Contents

    Type 2 diabetes and pre-diabetes control, prevention, and reversal/remission

    Authors: Miles Hassell, MD & Shelly Johnson, MSN, RNC-MNN, NPD-BC. GreatMed.org.

    Literature review current through: 7/12/23. This topic last updated: 12/12/2023.

    This module is sponsored by the founding board members.

    Editorial policy

     

    Definition of Type 2 diabetes (See Type 2 Diabetes, The Basics, at UpToDate)

    The diagnosis of type 2 diabetes (DM2) is made in a variety of ways.  Most settings typically use a blood test called hemoglobin A1c (or HbA1c, glycosylated hemoglobin). The HbA1c test usually reflects average blood glucose for roughly the past two to three months. Diabetes is usually diagnosed at an HbA1c of greater than or equal to 6.5%.[1]

    Result A1c
    Normal less than 5.7%
    Prediabetes 5.7% to 6.4%
    Diabetes 6.5% or higher

     

    Prediabetes is a condition in which the blood sugars are elevated above normal, but not high enough to meet criteria for DM2. Because patients with prediabetes share many of the same risks of long-term organ dysfunction as those with DM2, vigorous treatment of prediabetes, using lifestyle interventions, should be considered.

    Making sense of related terms such as pre-diabetes, DM2, metabolic syndrome, insulin resistance, impaired insulin secretion, and beta cell dysfunction

    The path toward prediabetes and DM2 is often first recognized as increasing components of metabolic syndrome (abdominal obesity, high blood pressure or treated blood pressure, high triglycerides, low HDL cholesterol and elevated blood sugar) occur. As the body produces greater amounts of the hormone insulin to control blood sugars (insulin resistance), blood sugar rises further. The beta cells in the pancreas (the organ that makes insulin) often begin to fail and insulin production falls, leading to higher blood sugars and typically the need for medications, including insulin injections.[2] Blood glucose is a measurement or marker by which insulin resistance is assessed.  It is one of several markers, and can be a useful signal of other harms; however, lowering a blood glucose lab level is not the overall goal, as it alone is not a reliable marker of improving patient outcomes. Lifestyle approaches treat insulin resistance in order to bring down blood glucose levels as hundreds of other metabolic processes are improved, rather than focusing on glucose alone.

    Incidence

    As of 2017, about 10% of the U.S. population has DM2,[3] while more than 84 million adult Americans (1 in 3) are estimated to have prediabetes.[4] As of 2019, 9.3% of the world’s population (463 million) has diabetes.[5] The U.S. spends over $327 billion on diabetes annually, not including the care demands of associated comorbidities.[6]

    Characteristics predisposing people to developing prediabetes and DM2

    Predisposition is multifactorial, including being overweight, less physical activity, highly processed food in the diet, family history, environment, and other factors. Excess central body weight and physical inactivity dominate the current risk factor literature.[3][5][10][11][13] It is often helpful to identify those with two or more elements of the metabolic syndrome as being at higher risk of developing diabetes. The elements of the metabolic syndrome include abdominal obesity, high blood pressure or treated blood pressure, high triglycerides, low HDL cholesterol and elevated blood sugar.

    What is the difference between Type 1 (DM1) and Type 2 diabetes (DM2)?

    This lifestyle guide focuses on DM2, the most common type of diabetes in adults (>90%), typically distinguished by high amounts of sugar circulating in the blood, often due to progressive loss of insulin secretion from the beta cells on top of insulin resistance, resulting in relative insulin deficiency.[7]  With the presence of more routine screening, people with DM2 and prediabetes have been identified sooner, giving clinicians and patients an opportunity to implement lifestyle tools before seeing further evidence of harm.  Type 1 diabetes (DM1) is characterized by autoimmune damage to pancreatic beta cells, with typical onset in youth, leading to absolute insulin deficiency, accounts for approximately 5 to 10% of diabetes in adults; more information on Type 1 diabetes may be found at UpToDate and the American Diabetes Association.

    Do the lifestyle recommendations made for DM2 also help patients with DM1?

    Although the lifestyle strategies outlined here do not eliminate the need for insulin treatment of DM1, in clinical settings, these dietary recommendations do seem to reduce the amount of insulin that is needed, reduce blood sugar variability, and are associated with better health outcomes in general populations.  In a cross-sectional study in Portugal, 95 people with DM1 using continuous glucose monitoring and insulin pumps were asked to describe their exercise regimens, if they ate prior to exercise, and how their insulin needs changed during and after a bout of exercise.[8]  Those who exercised had less variation out of ideal range before, during, and up to 24 hours after exercise.[8] Those who didn’t exercise described fear of hypoglycemia as a barrier.[8] A systematic review and meta-analysis agreed that youth with DM1 who exercised regularly needed lesser amounts of insulin doses per day than those who did not.[9]

    Risks associated with DM2

    The harms associated with DM2 include premature death, heart attack and heart failure,[10] stroke,[10] kidney failure,[11] and dialysis,[11] vision loss, peripheral nerve injury, increased cancer incidence, higher risk of infections, osteoarthritis, and surgical complications.[10] Patients with prediabetes may also share these risks. An increase in BMI of 5 kg/m2 from the upper limit of normal BMI (25 kg/m2) to the threshold of obesity (30 kg/m2) more than doubles the risk of death associated with DM2.[12]

    Health risks associated with DM2, such as heart attacks and stroke are elevated early in the disease process, often even before DM2 is diagnosed by typical criteria, so it is reasonable to explore lifestyle tools to prevent progression of the disease as early as possible, when prediabetes or metabolic syndrome are first identified.  Early in the disease process, patients may have mild hyperglycemia that goes unnoticed as the pancreas compensates for higher sugar levels by secreting more insulin, potentially masking the effects of insulin resistance.  It is important to caution patients with central obesity or high blood pressure about the metabolic changes leading to DM2 that may be occurring, as eventually, beta cells are unable to keep up with the demand for insulin, and only then will rising blood sugars be recognized.[12]  These patients should be warned not to wait until their blood sugars are high enough to meet formal DM2 criteria; they should be offered lifestyle-based risk reduction early and often.

    Presentation of DM2 and prediabetes

    Although most patients with prediabetes and DM2 have no symptoms prior to diagnosis and are found on routine screening, some patients with DM2 may present with frequent urination, persistent thirst, extreme fatigue, blurry vision, slow-healing wounds, and neuropathy symptoms such as tingling, pain, or numbness in the hands/feet.[13] Others are found when the patient presents with a complication such as heart disease, stroke, kidney failure or an abnormal eye exam.

    Pharmaceutical management (medications): do they reduce risks and costs associated with DM2?

    There are many different types of oral and injectable medications to treat DM2, and many of these medications do reduce risks associated with DM2, but they do not appear to reduce the risks associated with DM2 to the low level of risk of a person without diabetes.[14] While many patients need to use medications for their DM2, people often find they can reduce or eliminate the use of those medications by vigorously adopting lifestyle choices aimed at reversing type two diabetes, prediabetes, and associated risk factors.[15]

    Lifestyle strategies for preventing and reversing DM2, insulin resistance and metabolic syndrome

    Using lifestyle choices to improve disease is attractive because it typically means better health overall, fewer medications, lower healthcare costs, and reduced risk of catastrophic complications associated with diabetes, such as stroke.[16] The problems and practical lifestyle solutions related to this preventable disease have been well-documented from the days of Hippocrates. In 1816, surgeon William Wadd (who documented his own disease reversal from eating more vegetables and adding strenuous rowing exercise) expressed frustration that more general practitioners do not sufficiently regard Hippocrates’ notion that “all great changes of constitution are more likely to be effected by alterations of diet and modes of life, than by medicine”…and [diet] “affords hope and consolation to the patient, in a disease where medicine is known to be unavailing, and surgery affords no more than a temporary relief.”[17]

    Defining DM2 remission and reversal

    Remission: The American Diabetes Association and other international organizations define DM2 remission as having a HbA1c of less than 6.5% for at least 3 months without blood sugar medication.[18]

    Reversal: There is less agreement on the use of the term DM2 reversal. One way to define reversal is achieving a HbA1c of less than 6.5% (for diabetes reversal) or 5.8% (for prediabetes reversal) for one year without the use of blood sugar lowering medications. As stated above, the American Diabetes Association (ADA) defines remission as sustaining normal blood glucose levels (HbA1c <6.5%) for at least three months without taking diabetes pharmaceuticals.1 Partial remission of DM2 has been defined by the diabetes community as HbA1c of 5.7-6.5% while complete remission or reversal has been defined (as above) as HbA1c of <5.7% without the need for medication.[19]  Whether called reversal or remission, most can agree that reducing risk for diabetes-related complications is a good thing.

    Can everyone with DM2 who vigorously applies lifestyle medicine methods fully reverse their DM2? Likely not. However, in practice, it appears that those patients who employ minimally processed diets, physical activity, and other healthy lifestyle choices methods often reverse their DM2, seem to become healthier overall, require few medications, lower their risk factors, and achieve a better sense of their own healthcare agency and well-being.

    What does the peer-reviewed literature show about lifestyle and DM2?

    Studies applying lifestyle tools for reversal/remission of DM2

    Patients with diabetes are at increased risk of dozens of disorders, including about 6 years shorter life expectancy, largely due to higher risk of cardiovascular disease and cancer.[20] Therefore, it is important to emphasize therapeutic efforts that have been shown to reduce complications and death while increasing quality of life, not just aim for better blood sugar control. Treatment of obesity and unhealthy weight is not additional or complementary to basic medical care; it is the standard. The American Diabetes Association (ADA) emphasizes lifestyle before discussing pharmacotherapy in its standards of care; they emphasize that for patients with diabetes and obesity, a sustained, >10% weight loss, usually translates into possible remission of DM2 and may improve long-term cardiovascular outcomes and mortality.[71]

    DiRECT trial

    DiRECT is an open-label, cluster-randomized study. 306 adults aged 20-65 years old who were overweight (BMI 27-45) with DM2 were randomized to either a weight management program or guideline-directed standard practice care control group. The weight loss group started a very low calorie diet for 3-5 months, followed by structured support for long-term weight loss.21 46% of the overall weight-loss group achieved diabetes remission; remission was achieved by only 4% of those in the control group.[21] Of those who lost 15kg (33lbs) or more, 86% achieved diabetes remission at 12 months, and 70% remained in remission at 24 months, and quality of life improved in the weight loss group, and declined in the control group.[21]

    Look AHEAD trial

    In the Look AHEAD (Action for Health in Diabetes) trial, 5,145 adults with a mean age of 60, who had DM2 for an average of 6.8 years, were randomized to one group focusing on lifestyle intervention involving group and individual meetings, and another group focused on diabetes education.[22] The lifestyle group aimed for improving food and exercise habits.[22] These habits centered around reducing overeating, keeping a food log, eating more fruits and vegetables, and including other high-fiber foods that are nutrient-rich and lower in energy-density.  This followed the idea that satiation may be achieved when consuming a greater quantity of whole foods without feeling deprived.[22] The exercise portion of the lifestyle group aimed for 175 min of moderate-intensity physical activity per week.[22] These participants also met weekly with registered dietitians, behavioral psychologists, and exercise specialists.[19] These interdisciplinary specialists are potential champions in seeing lifestyle tools work and could be a catalyst for a substantial shift in the healthcare culture if encouraged to join physicians in the pursuit of population diabetes reversal. The lifestyle group lost 8.6% of their body weight at one year (compared to 0.7% in the control group). 11.5% had partial or complete diabetes remission after 5 years. The lifestyle group also decreased their mean HbA1c from 7.3 to 6.6% (compared to 7.3 to 7.2% in the control group), maintained lower HbA1c after 6 years, used fewer medications (including statins), had less albuminuria (protein in the urine, a marker of kidney damage), had better sleep, less depression, and better reported quality of life, physical functioning, sexual functioning, and mobility.[22]

    DIADEM-I trial

    The DIADEM-I randomized controlled trial, one of the first to focus on younger adults (age 18-50) with DM2, randomized 147 participants in the public health setting in Qatar.[23]  They directed an intensive lifestyle intervention group to replace their meals (with a provided lower-calorie meal replacement plus raw vegetables, salad, increased water, and fiber), to exercise for 150 minutes a week (walking was emphasized), and to stop their diabetes medications; and a control group to follow standard diet and activity advice and to continue their medications.[23] They found more diabetes remission for 61% of people in the intervention group compared with 12% in the control group.[23] The intervention group also lost more waist circumference, had more lean muscle mass, had lower blood pressure and less need for blood pressure drugs, less need for lipid-lowering drugs (a decrease from 31% to 26% of participants needing drugs in the intervention group vs. an increase from 40% to 76% of participants taking lipid-lowering drugs in the control group) at 12 months.[23] The intervention group also noticed a decrease in the total number of medications overall.[23]

    Worldviews on evidence-based practice in nursing meta-analysis

    A 2022 systematic review and meta-analysis of 12 studies involving 3997 patients, looked at lifestyle combinations of either a low- energy/low-calorie diet or a Mediterranean diet and habitual moderate intensity aerobic and resistance physical activity and/or walking.[24] The duration of lifestyle interventions varied from 12 weeks to 4 years.[24] The studies analyzed had a control group who received usual care (standard care or no intervention).[24] The primary outcome was the rate of diabetes remission, or absence of diabetes drugs with a normal HbA1c for 3 months.[24] The meta-analysis highlighted themes demonstrating how lifestyle intervention groups (most any combination of eating less and exercising more) demonstrated diabetes remission by almost four times compared to the control groups, had better quality of life, and had reduced weight compared to control groups.[24] The studies whose participants modified their diets (including those who followed a Mediterranean diet), and some moderate intensity exercise on most days of the week demonstrated diabetes remission, reduced weight, and improvement of quality of life.[24]

    The Stevenshof pilot study: Mediterranean diet and exercise

    In a Dutch primary care setting, an exploratory implementation study examined 15 adults who had T2D for more than 13 years were studied, measuring weight, waist/hip ratio, triglyceride levels, HbA1c, and other blood markers.[25] The clinical team, including doctors, nurse practitioners, and dieticians, met with patients to design personalized plans targeting diet, exercise, sleep, stress, and medication.[25] The first week, participants ate a very low-calorie diet of vegetables, then followed a low-carbohydrate Mediterranean diet with an 8-hour eating window.[25] Exercise was added dependent on the participant’s capacity.[25] Diabetes reversal was achieved in 4 participants at three months and maintained for 3 participants at 6 months with Mediterranean diet.26 When participants fell into their old habits, it was recommended they follow a vegetable diet for 2-4 days, or do intermittent fasting along with extra lifestyle coaching by a nurse practitioner or dietitian.[25]

    The REMIT pilot trial

    A randomized, open-label pilot trial out of Ontario, Canada followed 83 men and women with DM2 over 8 weeks as some participants focused intensely on weight loss, eating less and exercising more for 8 weeks, others focused on these habits for 16 weeks, and a control group received standard lifestyle advice and received a pedometer as incentive to be active.[26] The 8-week group showed a 44.4% partial or complete remission (based on HbA1C criteria) 52 weeks after starting the intervention.[39] The 16-week group showed 25.9% had either regression or remission 52 weeks after starting, and the control group showed 14.3% diabetes regression or remission.39 35.7% of the 16-week group achieved >/= 5% weight loss compared with 10.7% in the control group.[39]

    People with diabetes who are strongly motivated to see immediate results may be interested in the research on short-term very-low-calorie diets (VLCD).[39] A prospective, longitudinal, single-center study followed 30 people T2D for 6 months.[27]  The first 8 weeks, they ate very low calorie diets (VLCD); then they had a stepped return to a more balanced caloric intake that met their energy needs over 2 weeks.[40] Then, they followed a structured, individualized weight management program over 6 months.[40] Participants lost an average of 31 pounds during the study and kept most of it off after 6 months.[40] At 6 months, 40% of the participants achieved a normal fasting glucose without pharmaceuticals, serum insulin improvement (dropping an average of 12.8 mU/L), HbA1c improvement (from 7.1 to 5.8 mmol/mol), hepatic index improvement (by 1.4 points) blood pressure improvement (from an average of 142/91 to 128/82) and triglyceride improvement (dropping an average of 0.82 mmol/L).[40]

    Intermittent fasting

    Some studies show intermittent fasting to be comparable to continuous energy restriction when it comes to weight loss and reducing HbA1c.[28][29] In a randomized controlled trial of 72 adults with diabetes, participants followed a Chinese Medical Nutrition Therapy (CMNT) diet (5 fasting days followed by 10 days of reintroducing everyday food items such as wheat, barley, rye, and oats, with reduced glycemic loads, and carbohydrates, and increased unsaturated fatty acids). [30] After 3 months of this regimen, 50% of the intermittent fasting group and 2.8% of the control group reversed their need for diabetic pharmaceuticals.[30] The fasting group saw their A1C go from 7.65 to 5.66; the control group saw their A1C go from 7.50 to 7.87.30 Quality of life ratings of the intermittent fasting increased by 4.57 points compared with the baseline scores, but decreased by 1.77 points in the control group.[30]

    Ketogenic diets

    Recent systematic reviews and meta-analyses suggest some benefit from following a ketogenic approach.  Populations practicing a ketogenic (keto) diet have demonstrated greater reduction in HbA1c and body weight than populations in intermittent fasting and control groups.[31],[32] The Stanford Keto-Med randomized crossover trial directed 40 participants with DM2 to follow a ketogenic diet for 12 weeks and a Mediterranean diet for 12 weeks, in random order.[33] Both diets included non-starchy vegetables and avoided sugars and refined grains.[33] The Mediterranean diet included legumes, fruits, and whole, intact grains, whereas the keto diet (aiming to sustain nutritional ketosis by limiting carbohydrates to 20-50 g/day and keeping proteins to about 1.5 g/kg ideal body weight/day, with remaining kcals coming from fats) avoided them.[33] Participants had all meals and snacks delivered to them the first 4 weeks, then were encouraged to continue along the assigned model with recipe support, and were encouraged to eat until they were satiated, not necessarily to strictly reduce calorie intake.[33] HbA1c values reduced (-0.23) from baseline with both diets, but did not differ significantly between diets at 12 weeks.[33] When participants followed the keto diet, their triglycerides decreased by 16% (compared with a decrease of 5% for the Mediterranean group), though their LDL cholesterol was higher (+10% compared to -5%) and keto participants had lower intakes of fiber, folate, vitamin C, and magnesium.[33] Variability from assigned diet was greatest when participants were on the keto diet in the self-provided meals phase.33 12 week follow-up data (where participants could choose to follow whichever dietary pattern they preferred) suggested the Mediterranean approach was more sustainable.[33] Clinical concerns included an elevated ALT level, kidney infection, and exacerbation of eczema for participants during their keto interval.[33]

    Preventing DM2: selected papers

    Patients with Type 2 diabetes, and to a lesser degree those with prediabetes and metabolic syndrome, are at much higher risk of serious health problems than those without those risk factors.[28][29] The lifestyle approaches to prevention of DM2 largely mirror the approaches used for type 2 diabetes reversal.[34]

    The Da Qing IGT and Diabetes Study

    This study enrolled 110,660 patients and followed them for 6 years. Improvements in diet, exercise, and diet combined with exercise were associated with 31%, 46% and 42% reductions in developing diabetes.[35] Follow-up data at 30 years also found significant reductions in deaths and complications in the active treatment groups.[36]

    The Finnish Diabetes Prevention Study

    This study showed a 58% decrease in diabetes over 3 years among 522 patients with prediabetes, using a diet and exercise intervention and modest weight loss.[37] 13 year follow up showed sustained benefit.[38]

    The Diabetes Prevention Program

    This program randomized 3,150 prediabetic patients with a lifestyle intervention group using combined weight loss (7% of body weight) and an exercise program to show a 58% reduction in diabetes risk over 2.8 years.[39] At 10-year follow up, the lifestyle group continued to show a 34% reduction in diabetes incidence.[39] Improvement in diet quality as measured by the Alternate Healthy Eating Index (AHEI) was associated with significantly lower risk of developing diabetes, and this risk reduction was largely independent of weight loss.[40]

    Mediterranean and DASH patterns

    Mediterranean diet patterns are strongly associated with reduction in DM2 risk, with a very large number of studies indicating risk reduction ranging from 19% to 52% in observational and randomized controlled studies, typically without a formal physical activity or weight loss component.[41] A similar diet approach, the DASH diet (Dietary Approaches to Stop Hypertension), which promotes whole foods and limits fat and sodium, is also associated with about a 20% reduction in DM2 incidence.[42] Eating patterns that follow a whole foods approach, emphasizing preparing meals at home, seem to consistently support people in avoiding preventable DM2-related harms. Although the data are less robust, vegetarian diets appear to be associated with less DM2.[43] Plant-predominant or plant-forward diets as a component of lifestyle improvement may stabilize or even reverse DM2 and cardiovascular disease.[44]

    Low-fat diets

    A two-arm randomized controlled study followed overweight, middle-aged men and women with DM2 over 4 years.[45]  Participants were randomized to eat a low-carbohydrate Mediterranean diet (n = 108) or a low-fat diet (n=107).[42] After 4 years, the patients who ate the Mediterranean diet showed a greater reduction of HbA1c, better diabetes remission (9.7% of the Mediterranean group had no diabetes 3 years later; 2.0% of the low-fat stayed diabetes-free), and needed 26% less pharmaceuticals as the group who ate a low-fat diet.[42] When studying sustainable diets, consider outcomes like the 5 years later data from this study: 5.8% those who followed the Mediterranean pattern stayed diabetes-free, whereas all the low-fat diet participants returned to a diabetic state.[46] In the Prevencion con Dieta Mediterranea (PREDIMED) trial, participants who reduced their intake to less than 30% of calories from fat, as compared with patients who did not reduce their total fat intake, did not have a reduction in cardiovascular events.[43] This is consistent with the results for low-fat diets in Look AHEAD[47] and other trials. Low-fat diets seem hard to stick with and nutritional quality may be overlooked when prioritizing fat reduction. Reducing refined carbohydrates shows to be more effective than reducing fat intake in systematic reviews,[48] and may be associated with better cognitive health.[49]

    Do lifestyle interventions for reversing or preventing DM2 improve health outcomes?

    Return of pancreatic function with diabetes reversal

    A major factor in the progression of diabetes is the loss of pancreatic beta cell function, the cells that make insulin, over time. When aiming for DM2 reversal, goals can include normal HbA1c as well as return to normal first-phase insulin response without pharmaceutical therapy.[39] DiRECT and other studies suggest that pancreatic function can be restored with lifestyle medicine. The Diabetes Remission Clinical Trial (DiRECT) performed detailed metabolic studies on a subgroup. In the intervention group, liver fat content decreased significantly immediately after weight loss.[50] Similarly, plasma triglyceride and pancreas fat content decreased whether or not glucose control normalized.[50] Recovery of first-phase insulin response defined those who returned to non-diabetic glucose control, sustained at 12 months[50] and was more common in those who had shorter diabetes duration overall.[50] This study demonstrated that beta cell ability to recover long-term function persists after diagnosis, and suggests that earlier intervention (such as by applying lifestyle methods when pre-diabetes or diabetes are first identified) will increase the chance of long-term success.[50] Supporting this concept, a Newcastle University study that followed 30 volunteers for 6 months who had DM2 for up to 10 years, showed that sustained weight loss (particularly, visceral fat loss) was associated with a return to normal insulin production.[51]

    ARIC study: less cardiovascular and all-cause death

    In a community-based cohort study (ARIC) following 3,804 adults with diabetes, adherence to a Mediterranean diet using a Mediterranean diet scale was associated with lower risk of cardiovascular events, cardiovascular death, and all-cause mortality over a 26-year follow-up, potentially reducing the healthcare burden of DM2.[52]

    Pregnancy complications, including gestational diabetes, and the Mediterranean diet

    Some of the most important outcomes in a healthy society include pregnancy and childbirth outcomes.  In the nuMoM2b multicenter cohort study, 10,038 women were followed from soon after conception of their first pregnancy through delivery.[53] Lifestyle and medical data were collected, and adherence to Mediterranean diet was measured using an aMed score.[53] Mediterranean diet pattern was found to be associated with lower risk of developing any adverse pregnancy outcome including preeclampsia/eclampsia, pregnancy-related hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, and even stillbirth, with evidence of a dose-response association.[53]

    Given the worrisome association between obesity, type 2 diabetes and breast cancer, it is notable that better blood sugar control in diabetic women with breast cancer is associated with better prognosis, including significantly lowering the risk of all-cause and breast-cancer specific mortality.[54] Good glycemic control is associated with a better prognosis in breast cancer patients with type 2 diabetes mellitus.[54]

    Additional major lifestyle tools for type 2 diabetes

    Exercise

    Physical activity has a large role in improving health outcomes in almost all patients, and the role of exercise for DM2 is particularly important. The Look AHEAD trial evaluated an intensive lifestyle intervention over 4 years in people with type 2 diabetes, and included accelerometry for objective evaluation of physical activity.[55] They found that those who were assigned to increased physical activity lowered their HbA1c by at least 0.6%, and about 0.9% for those that primarily exercise in the afternoon.[55] The use of intensive exercise also strongly increased the odds of discontinuing diabetes medications.[55] This study points out the potential for the timing of exercise to have greater benefit. Supporting this concept, exercise appears to favorably alter appetite in those with DM2.[55] Resistance exercise 20-30 minutes before or 45 minutes after a meal reduced the perception of hunger and increased fullness.[56]

    The UK Biobank prospective cohort study looked at the relationship between habitual exercise measured by accelerometer in 40,431 participants and development of DM2 over 6.3 years.[57] They found that any exercise was better than none, with >600 minutes per week of moderate physical activity being associated with 71% less DM2, while >75 minutes weekly of vigorous physical activity was associated with 64% less DM2.57 Only a small amount of the DM2 risk reduction was associated with lower weight.[57]

    While exercise by itself is a poor tool for weight loss, exercise can amplify the metabolic benefits of calorie restriction. For example, the INFINITE study is a 20-week study of 180 obese people age 65-79 years.[58] Their findings suggested a combination of moderate or intensive exercise with moderate calorie reduction was associated with improved glucose control, fatigue and fitness.[58]

    Exercise in small doses

    A literature review found shorter duration exercise (even ten minutes a day, most days of the week) that produced labored breathing and perspiration was related to better cardiovascular fitness, long-term exercise engagement, better blood sugar levels, less visceral fat, and had no adverse outcomes.[59] Any exercise two or three times a day may improve post-meal glucose levels and lipid profiles more than a similar volume of exercise once a day.[59] Short-duration exercise outcomes data are encouraging.  A prospective study of 71,893 adults looked at short-duration exercise, in episodes as short as 2 minutes, in as little as 15-20 minutes a week, and found 16-40% lower cancer mortality, all-cause mortality, and cardiovascular disease related mortality after following participants for five years.[60]

    Sleep

    A large body of epidemiologic evidence has linked insufficient sleep duration and quality to the risk of obesity, insulin resistance and DM2.[60][61] Obstructive sleep apnea should be screened for and addressed, as it may contribute substantially to DM2 risk; people with difficulty maintaining or initiating sleep have slightly less risk than those with family history of DM2, but greater risk than those with sedentary lifestyle.[61] A review of 14 sleep restriction studies showed less sleep resulted in changes in appetite-regulating hormones, increased hunger, increased caloric intake, weight gain, insulin resistance and elevated diabetes risk, and altered glucose metabolism.[62] A secondary analysis of a correlational study of 64 adults age 50 and over who had DM2 for over a year studied  sleep and eating behavior for 8 days using food and sleep diaries.[63] Patients with higher morning fatigue were more likely to report uncontrolled eating and emotional eating during the day; patients with better sleep quality were less likely to report uncontrolled emotional eating during the day.[63] Higher fatigue was also related to larger variations in snacking behavior.[63] Complex sleep issues like obstructive sleep apnea may be improved with lifestyle, thus removing a diabetes risk factor.  The INTERAPNEA parallel-group open-label randomized clinical trial studied 89 Spanish overweight/obese men with moderate to severe obstructive sleep apnea on continuous positive air pressure (CPAP) therapy for 8 weeks.  The group who focused on weight loss and lifestyle intervention (increasing whole fruits, vegetables, legumes, nuts, and whole grains, and reducing sugar; walking with supported sessions with an emphasis on increasing steps by 15% a week; and sleep hygiene education) significantly improved OSA severity and other outcomes (including -6.9kg weight loss for the lifestyle intervention group compared to -1.2kg weight loss for the control group) compared with usual care alone. At 8 weeks, 45% of participants in the intervention group no longer required CPAP therapy; at 6 months, 62% of participants in the intervention group no longer required CPAP.[90] The intervention group also lowered their blood pressure over 6 months to the point the authors estimated they had lowered their risk of stroke death by 40% and risk of death from ischemic heart disease or other vascular issues by 30%.[90] Lifestyle is suggested as a primary treatment for obstructive sleep apnea for overweight people because of its impact on other diabetes-related outcomes.  While there is some evidence that CPAP may help regulate blood sugars,[92][93] it is unclear if CPAP alone improves DM2 complications.  A 52-week randomized clinical trial of patients with obstructive sleep apnea and diabetic kidney disease randomized 185 patients to CPAP and usual care (n = 93) or usual care alone (n = 92) to see if CPAP helped reduce albuminuria.[91] Prescribed CPAP did not result in a statistically significant reduction in albuminuria.[91]

    Supplements

    Vitamin D supplementation is associated with lower diabetes risk in randomized, controlled studies, although the optimal dose is unknown a blood level of >50ng/ml was associated with the greatest benefit.[61] A cross-sectional study of 205 adults with DM2 measured vitamin D levels and found those who had >5 hours of to sunlight exposure had higher vitamin D levels and lower high-sensitivity C-reactive protein (or hs-CRP, a marker used to assess cardiac risk) levels compared with those who spent less time in the sun.[62] Their study suggested those who exercised more had higher vitamin D levels and lower urinary albumin/creatinine ratios (used to asses kidney damage), suggesting a protective effect from outdoor exercise over cardiovascular disease and nephropathy. A meta-analysis, however, compared observational estimates of the association between Vitamin D 25 (OH) metabolites and incident DM2 with Mandelian randomization estimates based on genetic instruments, and had conflicting findings for a link with DM2 and vitamin D levels, and did not support the use of vitamin D supplementation for preventing DM2.[63]

    Cinnamon (cassia [common kitchen variety including Chinese and Saigon] and Ceylon [more expensive, referred to as “true” cinnamon]) has been studied in doses of 1-2 grams daily, divided into 2-3 mealtime doses, showing mixed evidence for benefit in recent studies.  Ceylon cinnamon was used in a small study of 132 adults with DM2 at 1,500mg once daily on an empty stomach for 4 months, showing greater reductions in fasting blood sugar (-35mg/dL vs. -5mg/dL) as well as reductions in HbA1c (-0.85% vs. +0.15%) in the test group.[64] A Portuguese randomized controlled trial of 36 adults with DM2 found that 6 grams of cassia cinnamon extract (made from soaking burmannii bark sticks), ingested prior to a glucose tolerance test, did not reduce blood sugar response compared to a control group.[65] Several other trials suggest cinnamon may be effective at reducing blood sugar, but a Cochrane review looked at ten randomized controlled trials and found insufficient data to report significant changes in HbA1c, increased health-related quality of life, morbidity, mortality, or costs.[66] As current literature demonstrates vast variations in glucose testing and cinnamon formulations as well as variations in outcomes, and adverse events are recorded (including stomach upset, constipation, hives, cramps, acute hepatitis and dermatitis),[67] recommending flavoring food with cinnamon to the amount it is pleasurable for eating may be a way to encourage patients to continue to enjoy the benefits of preparing their own meals while avoiding potentially toxic doses.

    Magnesium may deserve honorable mention as observational studies suggest higher magnesium intake is associated with a decreased risk of type 2 diabetes and stroke, according to a systematic review and meta-analysis.[68] Whether magnesium supplements are significantly helpful is uncertain, the benefit may be limited to those who consume foods rich in magnesium, such as greens and nuts.

    Apple cider vinegar (ACV) may be a useful lifestyle tool in lowering HbA1c, blood sugar, and weight.[72] Vinegar’s wellness-enhancing properties have been mentioned in the Bible; it was prescribed by Hippocrates for many ailments, and was used by Japanese samurai and other warriors for strength and as an antiseptic; and there are many other historical wellness references.[73] ACV is extracted after two fermentations of crushed apples and has been used for medicinal purposes throughout history due to its therapeutic properties, including those that facilitate the movement of carbohydrates through the gastrointestinal tract via suppression of digestive enzymes and helping convert glucose into glycogen.[74] Many randomized controlled trials reveal significant benefits, even greater than those that medications provide, including reduction in blood sugar levels (reducing HbA1c by up to 1.92 points in a 2015 randomized control trial [74]), less insulin resistance, better triglycerides, more weight loss, diabetes medications working better, better sports performance, and better lipid levels for study groups using ACV.[70][71][73][75]

    Organizing a comprehensive approach to reverse or prevent type 2 diabetes, reverse insulin resistance, and metabolic syndrome

    Treatment goals

    Personalized goals can include a basket of markers, typically including weight, waistline, fitness level, sense of well-being, blood pressure, glycosylated hemoglobin (HbA1C), urine microalbumin and the quantity of prescription medication as measurement tools to evaluate treatment progress. Improvements in these markers are typically predictive of improved long-term health outcomes.[69]

    When is the best time to start a DM2 or prediabetes reversal program using lifestyle?

    The serious health consequences associated with diabetes increase in frequency rapidly when fasting blood sugars exceed 100mg/dl, which is well before DM2 is diagnosed.[10] In addition, the metabolic changes that appear to be the cause of damage to pancreatic beta cell function and insulin production also are present early in the disease course.[70] Therefore, it is optimal to use lifestyle changes as soon as there is evidence of prediabetes or DM2 in order to improve a broad range of long-term health outcomes as well as preserve beta cell and overall organ function. Having risk factors such as high blood pressure, ‘prediabetic’ blood sugars, high triglycerides, excessive waistline, or a low fitness level are all warning signs that indicate lifestyle approaches are likely to be valuable to improve long-term health.

    Patient education

    Over 85% of people with DM2 are overweight or obese.[71] Realistic weight loss, especially reducing waist circumference, can delay the progression from prediabetes to DM2, improve blood sugar markers, reduce the amount of medications needed, and has been shown to sustain diabetes reversal through 2 years and beyond.[71][72] Guidelines from diabetes associations, international societies, and expert summits emphasize the importance of structured education to optimize lifestyle, promote self-management, and engage in shared decision making, aiming for prevention of multi-system complications.[73][74][75][76] Though barriers (including time constraints) persistently prevent these guidelines from materializing in the clinical setting.[77][78] engaging the interdisciplinary team with basic touch points (i.e. nurse phone calls) can help teams overcome time barriers, promote top of scope care, and improve biomarkers and overall health outcomes.[79][80][81]

    Components of patient dialogue can include

    • Address overweight/obesity: How did the patient get to this point, and what clues from the past indicate how to get to a healthier place?
    • What is being measured?
    • Motivations: What does the patient want their life to look like in 5 years?
    • Risks of disease progression and expectations for quality of life
    • Frank discussion of intensive lifestyle modification and its benefits
    • Pharmacologic therapy and its side effects
    • Psychological/spiritual interventions
    • Relevant generational/gestational risks
    • Benefits to other members of the patient’s household and social circle if they improve their own health; the ripple effect

     

    Disclaimer: This generalized information is a limited summary of evidence-based lifestyle tools. It is not meant to be comprehensive and should be used as a tool to help providers and patients understand and/or assess potential lifestyle treatment options. It does not include all information about conditions, treatments, pharmaceuticals, side effects, or risks that may apply to a specific patient; nor is it intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients should speak with a health care provider for complete information about their conditions, medical questions, and treatment options, including any risks or benefits regarding use of lifestyle tools and how they may compliment their pharmaceutical regimen. This information does not endorse any treatments or pharmaceuticals as safe, effective, or approved for treating a specific patient. The Comprehensive Risk Reduction Foundation and its affiliates disclaim any warranty or liability relating to this information or the use thereof. All rights reserved.

    Topic 1 Version 2.0

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